Bipolar Disorder, Alcohol Dependence
Conditions
Keywords
Alcoholism Bipolar Disorder Pharmacotherapy Naltrexone
Brief summary
The purpose of this study is to test the efficacy of naltrexone and valproate in the treatment of comorbid bipolar disorder and alcohol dependence.
Detailed description
Bipolar disorder has the highest rate of association with alcohol and other substance use disorders. This complex clinical presentation is asociated with severe disabilities,morbidity and heightened risk for suicide. There is a significant gap in our knowledge regarding effective treatment interventions for this high risk clinical population. This proposal will test the efficacy of a promising pharmacological approach for the treatment of comorbid alcohol dependence and bipolar disorder. We propose a randomized, double blind, placebo controlled 12-week trial to test the efficacy of valproate plus naltrexone vs. valproate alone in decreasing alcohol use and stabilizing mood symptoms among patients with comorbid alcohol dependence and bipolar disorder. All participants receive supportive psychosocial treatment.
Interventions
Naltrexone hydrochloride 50 mg capsule daily for 12 weeks
OTHERPlacebo
Placebo arm
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects will meet Diagnostic and Statistical Manual-IV (DSM-IV) criteria for current alcohol dependence and a concurrent bipolar disorder
Exclusion criteria
* 1\) Schizophrenia, schizoaffective and any nonbipolar psychotic disorder, unipolar major depression, primary anxiety disorder,mental retardation and signs of impaired cognitive functioning. * 2\) Opiate dependence, abuse, or on opioid maintenance treatment for any reason and those with positive urine screen for opiate. * 3)Current DSM-IV criteria for dependence on substances other that alcohol, cannabis,nicotine or caffeine. * 4\) Neurological conditions including epilepsy, history of brain injury,encephalitis or any organic brain syndrome or documented focally abnormal EEG. * 5)Medical conditions including severe cardiac, liver, kidney, endocrine, hematologic, or other impairing medical conditions, or impending surgery * 6)Pregnancy * 7)Inability or unwillingness to use contraceptive methods * 8)Any medical condition or other reason that in the opinion of the investigator would prevent the subject from completing the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Number of Standard Drinks Per Drinking Day During the Last 4 Weeks of the Trial | 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Subjects Abstinent | 12 weeks | Proportion of subjects abstinent during the last 4 weeks of the trial |
Countries
United States
Participant flow
Recruitment details
Sample drawn from University-based mental health services, community treatment programs and advertisement
Pre-assignment details
Total telephone screened included 696 inquiries: 517 excluded for not meeting initial screen criteria; 91 excluded for lost to follow-up with continuing screening; 88 enrolled into the study. Of the 88 enrolled, 35 excluded for not meeting the inclusion criteria; 35 were lost to follow-up before group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone Naltrexone add on to valproate open label
naltrexone add on to open label valproate: naltrexone 50 mg/day for 12 weeks add on to open label valproate | 9 |
| Placebo Placebo add on to valproate open label
Placebo add on to open label valproate for 12 weeks | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Total | Naltrexone | Placebo |
|---|---|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 10.9 | 42.3 years STANDARD_DEVIATION 9.5 | 41.7 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 6 Participants | 5 Participants |
| Region of Enrollment United States | 18 participants | 9 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 14 Participants | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 9 | 5 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
Mean Number of Standard Drinks Per Drinking Day During the Last 4 Weeks of the Trial
Time frame: 12 weeks
Population: One subject in the naltrexone group was considered an outlier and excluded from the analysis as it will disproportionally skew the results of small sample size, and one subject in the placebo group was lost to follow-up immediately after group allocation and before any first post allocation assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone | Mean Number of Standard Drinks Per Drinking Day During the Last 4 Weeks of the Trial | 0.6 standard drinks/drinking day | Standard Deviation 1.8 |
| Placebo | Mean Number of Standard Drinks Per Drinking Day During the Last 4 Weeks of the Trial | 3.8 standard drinks/drinking day | Standard Deviation 4.2 |
Secondary
% Subjects Abstinent
Proportion of subjects abstinent during the last 4 weeks of the trial
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naltrexone | % Subjects Abstinent | 66 percentage of participants |
| Placebo | % Subjects Abstinent | 33 percentage of participants |